Nanostructured carriers for guided and targeted on-demand substance delivery

Abstract

Methods, systems, and devices are disclosed for fabricating and implementing nanoscale and microscale structured carriers to provide guided, targeted, and on-demand delivery of molecules and biochemical substances for a variety of applications including diagnosis and/or treatment (theranostics) of diseases in humans and animals. In some aspects, a nanostructure carrier can be synthesized in the form of a nanobowl, which may include an actuatable capping particle that can be opened (and in some implementations, closed) on demand. In some aspects, a nanostructure carrier can be synthesized in the form of a hollow porous nanoparticle with a functionalized interior and/or exterior to attach payload substances and substances for magnetically guided delivery and controlled release of substance payloads.

What is claimed is: 
     
       1. A nanostructure device for carrying a payload, comprising:
 an interior particle structure that includes an opening to an internal cavity of the interior particle structure; 
 an exterior shell structure at least partially formed on an exterior surface of the interior particle structure; 
 a plurality of magnetic nanoparticles within the exterior shell structure; 
 a functionalization layer on a surface of the internal cavity capable of chemically attaching a molecular payload to the interior particle structure, 
 wherein the magnetic nanoparticles are structured to interact with an external magnetic field to magnetically steer the nanostructure device; and 
 a capping particle attached to the interior particle structure to cover the opening and enclose the molecular payload within the internal cavity, wherein attachment of the capping particle to the interior particle structure allows controllable movement of the capping particle to expose the opening based on a release stimulus, wherein the capping particle is attached to the interior particle structure by molecular self-assembly of a self-assembled monolayer (SAM) formed on the surface of the capping particle, or by a nucleic acid having two strands of a complementary sequence of nucleotides. 
 
     
     
       2. The device of  claim 1 , wherein the interior particle structure includes silica or the interior particle structure includes a size of substantially 200 nm or less. 
     
     
       3. The device of  claim 1 , wherein the magnetic nanoparticles include iron oxide nanoparticles or the magnetic nanoparticles include a size in a range of 5 to 15 nm. 
     
     
       4. The device of  claim 1 , wherein the exterior shell structure includes gold or the exterior shell structure includes a plurality of gold nanoparticles within the exterior shell structure. 
     
     
       5. The device of  claim 1 , further comprising:
 targeting ligand molecules conjugated to the interior particle structure, the targeting ligand molecules having an affinity to a receptor molecule found on a target cell to bind the interior particle structure to the target cell. 
 
     
     
       6. The device of  claim 1 , wherein the nanostructure device is operable to controllably release the molecular payload from the internal cavity to outside of the nanostructure device when a stimulus is applied to the nanostructure device to cause detachment of the molecular payload from the functionalization layer. 
     
     
       7. The device of  claim 1 , wherein the molecular payload includes at least one of a drug, image contrast agent, enzyme, protein, hormone, glycoprotein, glycolipid, nucleic acid, aptamer, lipid, or metallic, polymeric, or ceramic nanoparticle. 
     
     
       8. The device of  claim 1 , wherein the device is operable to controllably release the molecular payload by heating the nanostructure device to cause the controllable movement of the capping particle to expose the opening of the interior particle structure. 
     
     
       9. A nanostructure device for carrying a payload, comprising:
 an interior particle structure that includes an opening to an internal cavity of the interior particle structure; 
 an exterior shell structure at least partially formed on an exterior surface of the interior particle structure; 
 a plurality of magnetic nanoparticles within the exterior shell structure; 
 a functionalization layer on a surface of the internal cavity capable of chemically attaching a molecular payload to the interior particle structure, 
 wherein the magnetic nanoparticles are structured to interact with an external magnetic field to magnetically steer the nanostructure device; and 
 a capping particle attached to the interior particle structure to cover the opening and enclose the molecular payload within the internal cavity, wherein attachment of the capping particle to the interior particle structure allows controllable movement of the capping particle to expose the opening based on a release stimulus, 
 wherein the capping particle is attached to the interior particle structure by a molecular zipper structure, wherein the molecular zipper structure includes: 
 a double-stranded molecule including a hinge member attached at one end to a zipper member, the zipper member including a binding strand coupled to a passive strand, wherein the binding strand includes a sequence of nucleotide units hybridized with a corresponding complement sequence of nucleotide units of the passive strand, wherein the complement sequence of the nucleotides of the passive strand include one or more synthetic nucleobases; 
 a first arm member including a double-stranded molecular structure connected to the binding strand of the zipper member by a first linker strand that attaches the first arm member to the binding strand, and connected to the internal cavity; and 
 a second arm member including a double-stranded molecular structure connected to the passive strand of the zipper member by a second linker strand that attaches the second arm member to the passive strand, and connected to the capping particle. 
 
     
     
       10. A method to produce a nanostructure, comprising:
 forming an interior particle structure on a core particle, wherein the core particle is partially encased by the interior particle structure; 
 attaching nanoparticles to the exterior surface of the interior particle structure; 
 forming a coating on the exterior surface of the interior particle structure that covers at least some of the attached nanoparticles; 
 removing the core particle from the interior particle structure, wherein the removed core particle forms an internal cavity within and an opening from an external surface of the interior particle structures; 
 loading the internal cavity of the interior particle structure with a molecular payload; and 
 attaching a capping particle to the interior particle structure to cover the opening and contain the molecular payload within the internal cavity, wherein the capping particle is capable to be move under an external stimulus to expose the opening, 
 wherein the attaching includes:
 forming a self-assembled mono layer (SAM) the surface of the capping particle; and 
 conjugating the outward end of the SAM to the internal cavity, 
 
 or wherein the attaching includes:
 forming a nucleic acid having a two strands of a complementary sequence of nucleotides to the capping particle and the internal cavity, wherein a first strand is attached to the capping particle, and a complimentary second strand is attached to the interior cavity of the interior particle structure. 
 
 
     
     
       11. The method of  claim 10 , wherein the interior particle structure includes silica, the interior particle structure is formed in an asymmetric shape on the core particle, or the interior particle structure includes a size of substantially 500 nm or less. 
     
     
       12. The method of  claim 10 , wherein the core particle includes polystyrene or the polystyrene core particle is functionalized with a carboxylate-terminus coating. 
     
     
       13. The method of  claim 12 , wherein the polystyrene core particle is functionalized with a carboxylate-terminus coating or the polystyrene core particle includes a size of substantially 150 nm or less. 
     
     
       14. The method of  claim 10 , further comprising:
 prior to the attaching the nanoparticles, chemically modifying the external surface of the interior particle structure. 
 
     
     
       15. The method of  claim 10 , wherein the nanoparticles include one or both of iron oxide nanoparticles and metal nanoparticles. 
     
     
       16. The method of  claim 10 , wherein the forming the coating includes producing a filling material between at least some of the nanoparticles on the external surface of the interior particle structure. 
     
     
       17. The method of  claim 10 , wherein the attaching the nanoparticles includes facilitating an electrostatic interaction of the nanoparticles to the exterior surface of the interior particle structure. 
     
     
       18. The method of  claim 10 , further comprising:
 etching at least a portion of the interior particle structure within the internal cavity to remove material from the interior particle structure. 
 
     
     
       19. The method of  claim 10 , wherein the molecular payload includes at least one of a drug, image contrast agent, enzyme, protein, hormone, glycoprotein, glycolipid, nucleic acid, aptamer, lipid, or metallic, polymeric, or ceramic nanoparticle or wherein the loading includes functionalizing at least one of the external surface of the interior particle structure or internal surface of the internal cavity of the interior particle structure with attachment molecules capable of linking the molecular payload to the interior particle structure. 
     
     
       20. The method of  claim 10 , wherein the external stimuli includes radio frequency (RF) energy or near infrared (NIR) energy that causes the heating to uncover the capping particle from the opening. 
     
     
       21. A nanoparticle, comprising:
 a shell structured to include a hollow interior and one or more openings extending between the hollow interior and an exterior surface of the shell; 
 magnetic nanoparticles attached to one or both of the hollow interior or the exterior surface of the shell, wherein the magnetic nanoparticles are structured to interact with an external magnetic field to magnetically steer the nanoparticle; 
 a molecular payload attached to the shell by attachment molecules capable of linking the molecular payload to a surface of the shell; and 
 one or more capping particles attached to the shell to cover the one or more corresponding openings and enclose the molecular payload within the hollow interior of the shell, wherein attachment of the one or more capping particles to the shell allows controllable movement of the one or more capping particles to expose the one or more corresponding openings based on a release stimulus, wherein the one or more capping particles are attached to the shell by molecular self-assembly of a self-assembled monolayer (SAM) formed on a surface of the capping particle, or by a nucleic acid having two strands of a complementary sequence of nucleotides. 
 
     
     
       22. The nanoparticle of  claim 21 , wherein the magnetic nanoparticles include iron oxide nanoparticles. 
     
     
       23. The nanoparticle of  claim 21 , wherein the shell includes an outer layer formed around an inner layer. 
     
     
       24. The nanoparticle of  claim 21 , wherein the molecular payload includes at least one of a drug, image contrast agent, enzyme, protein, hormone, glycoprotein, glycolipid, nucleic acid, aptamer, lipid, and/or metallic, polymeric, or ceramic nanoparticle.